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Effects of Prolonged Growth Hormone Administration in Rats with Chronic Renal Insufficiency

机译:长期服用激素对慢性肾功能不全大鼠的影响

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Recombinant hGH (rhGH) augments short-term linear growth in experimental animals and children with chronic renal failure. Significant augmentation of final height, however, requires prolonged growth hormone therapy during years of growth. The effects of prolonged rhGH treatment on linear growth, progression of renal dysfunction, and longevity in the setting of renal insufficiency are unknown. We examined at 9, 15, and 25 wk growth in length and weight, glomerular filtration rate measured by inulin and creatinine clearance, food efficiency (g ingested/weight gained), and survival in treated (U-GH) and untreated (U) 75% nephrectomized uremic rats and in treated (S-GH) and untreated (S) sham-operated rats. We also measured kidney weight to body weight ratios at the time the rats were killed. Treatment was rhGH 1.0 mg s.c. three times a week during wks 4–12 of life. Length of U-GII rats was greater than that of U rats (p p versus S and S-GH rats.; by 15 wk, U-GH rat weight was equal to S rat weight. Glomerular filtration rate measured by creatinine was markedly reduced in U and U-GH rats and did not increase in response to prolonged rhGH in either U-GH or S-GH rats. Diminished food efficiency of U rats versus S rats (p versus U rats (p < 0.05). The growth-promoting effect of rhGH was observed late (rather than early) in the growth period. Prolonged rhGH treatment did result in U-GH rats attaining length and weight comparable to S rats, ameliorating the growth failure due to uremia. Glomerular filtration rate was not adversely affected by prolonged rhGH treatment, and there appeared to be significant renal growth with growth hormone administration as measured by kidney weight/body weight ratio. Survival data, however, suggest that the growth-stimulating effect of rhGH in uremic animals may be accompanied by a trend toward reduced longevity, and histologic evaluation revealed increased glomerular hypertrophy and glomerulosclerosis in both normal and uremic rats treated with rhGH.
机译:重组hGH(rhGH)增强了实验动物和患有慢性肾衰竭的儿童的短期线性生长。但是,最终身高的显着增加需要在多年的生长过程中延长生长激素治疗的时间。长期的rhGH治疗对线性生长,肾功能不全的进展以及肾功能不全的寿命的影响尚不清楚。我们检查了9、15和25周的长度和体重增长,通过菊粉和肌酐清除率测量的肾小球滤过率,食物效率(摄入的g /体重增加)以及治疗(U-GH)和未治疗(U)的存活率75%肾切除的尿毒症大鼠以及治疗的(S-GH)和未治疗的(S)假手术大鼠。我们还测量了大鼠被杀死时的肾脏重量与体重之比。处理为rhGH 1.0mgs.c。在每周4至12周内每周进行三次。 U-GII大鼠的长度大于U大鼠的长度(pp对S和S-GH大鼠。;到15周时,U-GH大鼠体重等于S大鼠体重。肌酐测量的肾小球滤过率显着降低U和U-GH大鼠在U-GH或S-GH大鼠中对rhGH的延长均无反应,U大鼠和S大鼠的食物效率降低(p对U大鼠(p <0.05)。在生长后期(而不是早期)观察到了rhGH的作用,延长rhGH治疗的确使U-GH大鼠达到了与S大鼠相当的长度和体重,减轻了尿毒症引起的生长衰竭,肾小球滤过率没有受到不利影响长期使用rhGH治疗后,以肾重/体重比衡量,服用生长激素后肾脏明显生长,但存活数据表明rhGH在尿毒症动物中的生长刺激作用可能伴随着趋势减少寿命拓扑学评估显示,在接受rhGH治疗的正常和尿毒症大鼠中,肾小球肥大和肾小球硬化增加。

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